title: Transmissible gastroenteritis virus infection induces cell cycle arrest at S and G2/M phases via p53-dependent pathway.
abstract: p53 signaling pathway plays an important role in the regulation of cell cycle. Our previous studies have demonstrated that TGEV infection induces the activation of p53 signaling pathway. In this study we investigated the effects of TGEV infection on the cell cycle of host cells and the roles of p53 activation in this process. The results showed that TGEV infection induced cell cycle arrest at S and G2/M phases in both asynchronous and synchronized PK-15 and ST cells, while UV-inactivated TGEV lost the ability of induction of cell cycle arrest. TGEV infection promoted p21 accumulation, down-regulated cell cycle-regulatory proteins cyclins B1, cdc2, cdk2 and PCNA. Further studies showed that inhibition of p53 signaling could attenuate the TGEV-induced S- and G2/M-phase arrest by reversing the expression of p21 and corresponding cyclin/cdk. In addition, TGEV infection of the cells synchronized in various stages of cell cycle showed that viral genomic RNA and subgenomic RNA, and virus titer were higher in the cells released from S-phase- or G2/M phase-synchronized cells than that in the cells released from the G0/G1 phase-synchronized or asynchronous cells after 18h p.i. Taken together, our data suggested that TGEV infection induced S and G2/M phase arrest in host cells, which might provide a favorable condition for viral replication.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China; College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Meiling
authors.initials: M
authors.lastname: Dai
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhao
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.forename: Feng
authors.initials: F
authors.lastname: Dong
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Ruichao
authors.initials: R
authors.lastname: Huo
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.forename: Xingang
authors.initials: X
authors.lastname: Xu
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D002455:Cell Division; D002460:Cell Line; D054884:Host-Pathogen Interactions; D016196:S Phase; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Cell cycle arrest; TGEV; Virus replication; p53 pathway